tbuckley/cabot-search huggingface dataset:
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016—2020
Authors: Quinn T Ostrom, Mackenzie Price, Corey Neff, Gino Cioffi, Kristin A Waite, Carol Kruchko, Jill S Barnholtz-Sloan
Journal: Neuro-Oncology (2023)

Abstract The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.83 per 100,000 population (malignant AAAIR=6.94 and non-malignant AAAIR=17.88). This overall rate was higher in females compared to males (27.85 versus 21.62 per 100,000) and non-Hispanic persons compared to Hispanic persons (25.24 versus 22.61 per 100,000). Gliomas accounted for 26.3% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (14.2% of all tumors and 50.9% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (40.8% of all tumors and 56.2% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.13 per 100,000 population. There were 86,030 deaths attributed to malignant brain and other CNS tumors between 2016 and 2020. This represents an average annual mortality rate of 4.42 per 100,000 population and an average of 17,206 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.7%, for a non-malignant brain and other CNS tumor the five-year relative survival rate was 91.8%.
Definitions, End Points, and Clinical Trial Designs for Bladder Cancer: Recommendations From the Society for Immunotherapy of Cancer and the International Bladder Cancer Group
Authors: Ashish M. Kamat, Andrea B. Apolo, Marek Babjuk, Trinity J. Bivalacqua, Peter C. Black, Roger Buckley, Matthew T. Campbell, Eva Compérat, Jason A. Efstathiou, Petros Grivas, Shilpa Gupta, Neil J. Kurtz, Donald Lamm, Seth P. Lerner, Roger Li, David J. McConkey, Joan Palou Redorta, Thomas Powles, Sarah P. Psutka, Neal Shore, Gary D. Steinberg, Richard Sylvester, J. Alfred Witjes, Matthew D. Galsky
Journal: Journal of Clinical Oncology (2023)

There is a significant unmet need for new and efficacious therapies in urothelial cancer (UC). To provide recommendations on appropriate clinical trial designs across disease settings in UC, the Society for Immunotherapy of Cancer (SITC) and the International Bladder Cancer Group (IBCG) convened a multidisciplinary, international consensus panel.Through open communication and scientific debate in small- and whole-group settings, surveying, and responses to clinical questionnaires, the consensus panel developed recommendations on optimal definitions of the disease state, end points, trial design, evaluations, sample size calculations, and pathology considerations for definitive studies in low- and intermediate-risk nonmuscle-invasive bladder cancer (NMIBC), high-risk NMIBC, muscle-invasive bladder cancer in the neoadjuvant and adjuvant settings, and metastatic UC. The expert panel also solicited input on the recommendations through presentations and public discussion during an open session at the 2021 Bladder Cancer Advocacy Network (BCAN) Think Tank (held virtually).The consensus panel developed a set of stage-specific bladder cancer clinical trial design recommendations, which are summarized in the table that accompanies this text.These recommendations developed by the SITC-IBCG Bladder Cancer Clinical Trial Design consensus panel will encourage uniformity among studies and facilitate drug development in this disease.
Single‐Step Biofabrication of In Situ Spheroid‐Forming Compartmentalized Hydrogel for Clinical‐Sized Cartilage Tissue Formation
Authors: Bas van Loo, Maik Schot, Melvin Gurian, Tom Kamperman, Jeroen Leijten
Journal: Advanced Healthcare Materials (2023)

Abstract 3D cellular spheroids offer more biomimetic microenvironments than conventional 2D cell culture technologies, which has proven value for many tissue engineering applications. Despite beneficiary effects of 3D cell culture, clinical translation of spheroid tissue engineering is challenged by limited scalability of current spheroid formation methods. Although recent adoption of droplet microfluidics can provide a continuous production process, use of oils and surfactants, generally low throughput, and requirement of additional biofabrication steps hinder clinical translation of spheroid culture. Here, the use of clean (e.g., oil‐free and surfactant‐free), ultra‐high throughput (e.g., 8.5 mL min −1 , 10 000 spheroids s −1 ), single‐step, in‐air microfluidic biofabrication of spheroid forming compartmentalized hydrogels is reported. This novel technique can reliably produce 1D fibers, 2D planes, and 3D volumes compartmentalized hydrogel constructs, which each allows for distinct (an)isotropic orientation of hollow spheroid‐forming compartments. Spheroids produced within ink‐jet bioprinted compartmentalized hydrogels outperform 2D cell cultures in terms of chondrogenic behavior. Moreover, the cellular spheroids can be harvested from compartmentalized hydrogels and used to build shape‐stable centimeter‐sized biomaterial‐free living tissues in a bottom‐up manner. Consequently, it is anticipated that in‐air microfluidic production of spheroid‐forming compartmentalized hydrogels can advance production and use of cellular spheroids for various biomedical applications.
Novel Use of Circulating Tumor DNA to Identify Muscle-invasive and Non–organ-confined Upper Tract Urothelial Carcinoma
Authors: Heather L. Huelster, Billie Gould, Elizabeth A. Schiftan, Lucia Camperlengo, Facundo Davaro, Kyle M. Rose, Alex C. Soupir, Shidong Jia, Tiantian Zheng, Wade J. Sexton, Julio Pow-Sang, Philippe E. Spiess, G. Daniel Grass, Liang Wang, Xuefeng Wang, Aram Vosoughi, Andrea Necchi, Joshua J. Meeks, Bishoy M. Faltas, Pan Du, Roger Li
Journal: European Urology (2023)
European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia
Authors: Nicholas C. P. Cross, Thomas Ernst, Susan Branford, Jean-Michel Cayuela, Michael Deininger, Alice Fabarius, Dennis Dong Hwan Kim, Katerina Machova Polakova, Jerald P. Radich, Rüdiger Hehlmann, Andreas Hochhaus, Jane F. Apperley, Simona Soverini
Journal: Leukemia (2023)

Abstract From the laboratory perspective, effective management of patients with chronic myeloid leukemia (CML) requires accurate diagnosis, assessment of prognostic markers, sequential assessment of levels of residual disease and investigation of possible reasons for resistance, relapse or progression. Our scientific and clinical knowledge underpinning these requirements continues to evolve, as do laboratory methods and technologies. The European LeukemiaNet convened an expert panel to critically consider the current status of genetic laboratory approaches to help diagnose and manage CML patients. Our recommendations focus on current best practice and highlight the strengths and pitfalls of commonly used laboratory tests.
Autonomous artificial intelligence increases real-world specialist clinic productivity in a cluster-randomized trial
Authors: Michael D. Abramoff, Noelle Whitestone, Jennifer L. Patnaik, Emily Rich, Munir Ahmed, Lutful Husain, Mohammad Yeadul Hassan, Md. Sajidul Huq Tanjil, Dena Weitzman, Tinglong Dai, Brandie D. Wagner, David H. Cherwek, Nathan Congdon, Khairul Islam
Journal: npj Digital Medicine (2023)

Abstract Autonomous artificial intelligence (AI) promises to increase healthcare productivity, but real-world evidence is lacking. We developed a clinic productivity model to generate testable hypotheses and study design for a preregistered cluster-randomized clinical trial, in which we tested the hypothesis that a previously validated US FDA-authorized AI for diabetic eye exams increases clinic productivity (number of completed care encounters per hour per specialist physician) among patients with diabetes. Here we report that 105 clinic days are cluster randomized to either intervention (using AI diagnosis; 51 days; 494 patients) or control (not using AI diagnosis; 54 days; 499 patients). The prespecified primary endpoint is met: AI leads to 40% higher productivity (1.59 encounters/hour, 95% confidence interval [CI]: 1.37–1.80) than control (1.14 encounters/hour, 95% CI: 1.02–1.25), p &lt; 0.00; the secondary endpoint (productivity in all patients) is also met. Autonomous AI increases healthcare system productivity, which could potentially increase access and reduce health disparities. ClinicalTrials.gov NCT05182580.
Ablative radiation alone in stage I lung cancer produces an adaptive systemic immune response: insights from a prospective study
Authors: Khinh Ranh Voong, Peter B Illei, Bradley Presson, Dipika Singh, Zhen Zeng, Mara Lanis, Russell K Hales, Chen Hu, Phuoc T Tran, Christos Georgiades, Cheng Ting Lin, Jeffrey Thiboutout, Julie R Brahmer, Patrick M Forde, Jarushka Naidoo, Valsamo Anagnostou, Kellie N Smith
Journal: Journal for ImmunoTherapy of Cancer (2023)

Stereotactic ablative body radiation (SABR) delivers high rates of local control in early-stage non-small cell lung cancer (NSCLC); however, systemic immune effects are poorly understood. Here, we evaluate the early pathologic and immunologic effects of SABR. Blood/core-needle tumor biopsies were collected from six patients with stage I NSCLC before and 5–7 days after SABR (48 Gy/4 or 50 Gy/5 fractions). Serial blood was collected up to 1-year post-SABR. We used immunohistochemistry to evaluate pathological changes, immune-cell populations (CD8, FoxP3), and PD-L1/PD-1 expression within the tumor. We evaluated T-cell receptor (TCR) profile changes in the tumor using TCR sequencing. We used the MANAFEST (Mutation-Associated Neoantigen Functional Expansion of Specific T-cells) assay to detect peripheral neoantigen-specific T-cell responses and dynamics. At a median follow-up of 40 months, 83% of patients (n=5) were alive without tumor progression. Early post-SABR biopsies showed viable tumor and similar distribution of immune-cell populations as compared with baseline samples. Core-needle samples proved insufficient to detect population-level TCR-repertoire changes. Functionally, neoantigen-specific T-cells were detected in the blood prior to SABR. A subset of these patients had a transient increase in the frequency of neoantigen-specific T-cells between 1 week and 3–6 months after SABR. SABR alone could induce a delayed, transient neoantigen-specific T-cell immunologic response in patients with stage I NSCLC.
An mpox virus mRNA-lipid nanoparticle vaccine confers protection against lethal orthopoxviral challenge
Authors: Alec W. Freyn, Caroline Atyeo, Patricia L. Earl, Jeffrey L. Americo, Gwo-Yu Chuang, Harini Natarajan, Tiffany R. Frey, Jason G. Gall, Juan I. Moliva, Ruth Hunegnaw, Guha Asthagiri Arunkumar, Clinton O. Ogega, Arshan Nasir, Genesis Santos, Rafael H. Levin, Anusha Meni, Patricia A. Jorquera, Hamilton Bennett, Joshua A. Johnson, Michael A. Durney, Guillaume Stewart-Jones, Jay W. Hooper, Tonya M. Colpitts, Galit Alter, Nancy J. Sullivan, Andrea Carfi, Bernard Moss
Journal: Science Translational Medicine (2023)

Mpox virus (MPXV) caused a global outbreak in 2022. Although smallpox vaccines were rapidly deployed to curb spread and disease among those at highest risk, breakthrough disease was noted after complete immunization. Given the threat of additional zoonotic events and the virus's evolving ability to drive human-to-human transmission, there is an urgent need for an MPXV-specific vaccine that confers protection against evolving MPXV strains and related orthopoxviruses. Here, we demonstrate that an mRNA-lipid nanoparticle vaccine encoding a set of four highly conserved MPXV surface proteins involved in virus attachment, entry, and transmission can induce MPXV-specific immunity and heterologous protection against a lethal vaccinia virus (VACV) challenge. Compared with modified vaccinia virus Ankara (MVA), which forms the basis for the current MPXV vaccine, immunization with an mRNA-based MPXV vaccine generated superior neutralizing activity against MPXV and VACV and more efficiently inhibited spread between cells. We also observed greater Fc effector T
Multicellular bioprinted skin facilitates human-like skin architecture in vivo
Authors: Adam M. Jorgensen, Anastasiya Gorkun, Naresh Mahajan, Kelsey Willson, Cara Clouse, Claire G. Jeong, Mathew Varkey, Mingsong Wu, Stephen J. Walker, Joseph A. Molnar, Sean V. Murphy, Sang Jin Lee, James J. Yoo, Shay Soker, Anthony Atala
Journal: Science Translational Medicine (2023)

Bioprinting is a promising alternative method to generate skin substitutes because it can replicate the structural organization of the skin into biomimetic layers in vitro. In this study, six primary human skin cell types were used to bioprint a trilayer skin construct consisting of epidermis, dermis, and hypodermis. Transplantation of the bioprinted skin with human cells onto full-thickness wounds of nu/nu mice promoted rapid vascularization and formation of epidermal rete ridges analogous to the native human epidermis, with a normal-looking extracellular matrix. Cell-specific staining confirmed the integration of the implanted cells into the regenerated skin. Using a similar approach, a 5 centimeter–by–5 centimeter bioprinted autologous porcine skin graft was transplanted onto full-thickness wounds in a porcine excisional wound model. The bioprinted skin graft improved epithelialization, reduced skin contraction, and supported normal collagen organization with reduced fibrosis. Differential gene expression demonstrated pro-remodeling protease activity in wounds transplanted with bioprinted autologous skin grafts. These results demonstrate that bioprinted skin can support skin regeneration to allow for nonfibrotic wound healing and suggest that the skin bioprinting technology may be applicable for human clinical use.
A humanized chemogenetic system inhibits murine pain-related behavior and hyperactivity in human sensory neurons
Authors: Jimena Perez-Sanchez, Steven J. Middleton, Luke A. Pattison, Helen Hilton, Mosab Ali Awadelkareem, Sana R. Zuberi, Maria B. Renke, Huimin Hu, Xun Yang, Alex J. Clark, Ewan St. John Smith, David L. Bennett
Journal: Science Translational Medicine (2023)

Hyperexcitability in sensory neurons is known to underlie many of the maladaptive changes associated with persistent pain. Chemogenetics has shown promise as a means to suppress such excitability, yet chemogenetic approaches suitable for human applications are needed. PSAM 4 -GlyR is a modular system based on the human α7 nicotinic acetylcholine and glycine receptors, which responds to inert chemical ligands and the clinically approved drug varenicline. Here, we demonstrated the efficacy of this channel in silencing both mouse and human sensory neurons by the activation of large shunting conductances after agonist administration. Virally mediated expression of PSAM 4 -GlyR in mouse sensory neurons produced behavioral hyposensitivity upon agonist administration, which was recovered upon agonist washout. Stable expression of the channel led to similar reversible suppression of pain-related behavior even after 10 months of viral delivery. Mechanical and spontaneous pain readouts were also ameliorated by PSAM 4 -GlyR activation in acute and joint pain inflammation mouse models. Furthermore, suppression of mechanical hypersensitivity generated by a spared nerve injury model of neuropathic pain was also observed upon activation of the channel. Effective silencing of behavioral hypersensitivity was reproduced in a human model of hyperexcitability and clinical pain: PSAM 4 -GlyR activation decreased the excitability of human-induced pluripotent stem cell–derived sensory neurons and spontaneous activity due to a gain-of-function Na V 1.7 mutation causing inherited erythromelalgia. Our results demonstrate the contribution of sensory neuron hyperexcitability to neuropathic pain and the translational potential of an effective, stable, and reversible humanized chemogenetic system for the treatment of pain.
Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH)
Authors: Shuang Wang, Scott L.  Friedman
Journal: Science Translational Medicine (2023)

Metabolic dysfunction–associated steatohepatitis (MASH) is a severe form of liver disease that poses a global health threat because of its potential to progress to advanced fibrosis, leading to cirrhosis and liver cancer. Recent advances in single-cell methodologies, refined disease models, and genetic and epigenetic insights have provided a nuanced understanding of MASH fibrogenesis, with substantial cellular heterogeneity in MASH livers providing potentially targetable cell-cell interactions and behavior. Unlike fibrogenesis, mechanisms underlying fibrosis regression in MASH are still inadequately understood, although antifibrotic targets have been recently identified. A refined antifibrotic treatment framework could lead to noninvasive assessment and targeted therapies that preserve hepatocellular function and restore the liver’s architectural integrity.
Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events in Atherosclerotic Patients and Lesions
Authors: Guglielmo Gallone, Matteo Bellettini, Marco Gatti, Davide Tore, Francesco Bruno, Luca Scudeler, Vincenzo Cusenza, Antonio Lanfranchi, Andrea Angelini, Ovidio De Filippo, Mario Iannaccone, Luca Baldetti, Katia Audisio, Michelle Demetres, Gaetano Risi, Giulia Rizzello, Italo Porto, Paolo Fonio, Francesco Prati, Michelle C. Williams, Bon-Kwon Koo, Gianluca Pontone, Alessandro Depaoli, Peter Libby, Gregg W. Stone, Jagat Narula, Gaetano Maria De Ferrari, Fabrizio D’Ascenzo
Journal: JACC. Cardiovascular imaging (2023)
Proteomic Profiling in Patients With Peripartum Cardiomyopathy
Authors: Vitaris Kodogo, Charle Viljoen, Julian Hoevelmann, Graham Chakafana, Jasper Tromp, Hasan Ali Farhan, Sorel Goland, Peter van der Meer, Kamilu Karaye, Karolina Kryczka, Denise Hilfiker-Kleiner, Alice Jackson, Alexandre Mebazaa, Michael Böhm, Burkert Pieske, Johann Bauersachs, Liam Bell, Karen Sliwa
Journal: JACC Heart Failure (2023)
Identifying predictors of glioma evolution from longitudinal sequencing
Authors: Quanhua Mu, Ruichao Chai, Bo Pang, Yingxi Yang, Hanjie Liu, Zheng Zhao, Zhaoshi Bao, Dong Song, Zhihan Zhu, Mengli Yan, Biaobin Jiang, Zongchao Mo, Jihong Tang, Jason K. Sa, Hee Jin Cho, Yuzhou Chang, Kaitlin Hao Yi Chan, Danson Shek Chun Loi, Sindy Sing Ting Tam, Aden Ka Yin Chan, Angela Ruohao Wu, Zhaoqi Liu, Wai Sang Poon, Ho Keung Ng, Danny Tat Ming Chan, Antonio Iavarone, Do-Hyun Nam, Tao Jiang, Jiguang Wang
Journal: Science Translational Medicine (2023)

Clonal evolution drives cancer progression and therapeutic resistance. Recent studies have revealed divergent longitudinal trajectories in gliomas, but early molecular features steering posttreatment cancer evolution remain unclear. Here, we collected sequencing and clinical data of initial-recurrent tumor pairs from 544 adult diffuse gliomas and performed multivariate analysis to identify early molecular predictors of tumor evolution in three diffuse glioma subtypes. We found that CDKN2A deletion at initial diagnosis preceded tumor necrosis and microvascular proliferation that occur at later stages of IDH-mutant glioma. Ki67 expression at diagnosis was positively correlated with acquiring hypermutation at recurrence in the IDH-wild-type glioma. In all glioma subtypes, MYC gain or MYC-target activation at diagnosis was associated with treatment-induced hypermutation at recurrence. To predict glioma evolution, we constructed CELLO2 (Cancer EvoLution for LOngitudinal data version 2), a machine learning model integrating features at diagnosis to forecast hypermutation and progression after treatment. CELLO2 successfully stratified patients into subgroups with distinct prognoses and identified a high-risk patient group featured by MYC gain with worse post-progression survival, from the low-grade IDH-mutant-noncodel subtype. We then performed chronic temozolomide-induction experiments in glioma cell lines and isogenic patient-derived gliomaspheres and demonstrated that MYC drives temozolomide resistance by promoting hypermutation. Mechanistically, we demonstrated that, by binding to open chromatin and transcriptionally active genomic regions, c-MYC increases the vulnerability of key mismatch repair genes to treatment-induced mutagenesis, thus triggering hypermutation. This study reveals early predictors of cancer evolution under therapy and provides a resource for precision oncology targeting cancer dynamics in diffuse gliomas.
Maternal and Pregnancy Outcomes Following Heart Transplantation in the United States
Authors: Amanda M. Craig, Alexa Campbell, Sarah C. Snow, Toi N. Spates, Sarah A. Goldstein, Anna E. Denoble, Marie-Louise Meng, Jacob N. Schroder, Karen P. Flores, Richa Agarwal, Cary C. Ward, Jerome J. Federspiel
Journal: JACC Heart Failure (2023)